scholarly journals Role of matrix metalloproteinase in the aneurismatic aortic disease

2004 ◽  
Vol 62 (3) ◽  
Author(s):  
Nicola Troisi ◽  
Alfredo Mazza ◽  
Felice Mazza ◽  
Gabriele Iannelli
Keyword(s):  
Matrix Metalloproteinases ◽  
Aortic Disease ◽  
Endothelial Damage ◽  
Matrix Proteins ◽  
Tissue Destruction ◽  
The Matrix ◽  
Drug Inhibition ◽  
Atherosclerotic Aneurysm ◽  
Aneurysm Diameter

The aorta is involved in a large variety of diseases and the atherosclerotic aneurysms represent the most common type of these. Recent reports have attempted to clarify the mechanisms, that cause the formation and the progression of the atherosclerotic aneurysms, caused not only by the atherosclerosis. One of the features of this disease is the extensive proteolytic destruction of structural matrix proteins in the aortic wall realized by the matrix metalloproteinases. The atherosclerotic aneurysm can be considered a disease caused by an imbalance between connective tissue destruction and its repair. Knowledge of the role played by matrix metalloproteinases in the formation process of the aneurysms has made the inhibition of these proteins a logical therapeutic strategy. Once completed the aneurysm treatment, surgical or endovascular, the endothelial damage must disappear; the persistence of this damage, after endovascular procedure, is the cause of the formation of the endoleaks. The preoperative matrix metalloproteinases plasmatic levels are related to the aneurysm diameter and after endovascular treatment these values come back normal, except in the case of presence of an endoleak, that don’t make possible the reduction of these values. In spite of that, obscure points still remain, above all about the dosage of these proteins and their inhibition through drugs with clear metalloproteinases- inhibiting properties. The aim of this study is to clarify further on the mechanisms of the formation of the aneurysms with particular care to the matrix metalloproteinases, their dosage and their drug inhibition.

Matrix Metalloproteinases: Biologic Activity and Clinical Implications

2000 ◽  
Vol 18 (5) ◽  
pp. 1135-1135 ◽  
Author(s):  
Amy R. Nelson ◽  
Barbara Fingleton ◽  
Mace L. Rothenberg ◽  
Lynn M. Matrisian
Keyword(s):  
Matrix Metalloproteinases ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Metastatic Tumor ◽  
The Body ◽  
Genetic Changes ◽  
Biologic Activity ◽  
The Matrix ◽  
Degradative Enzymes

ABSTRACT: Tumor progression is a complex, multistage process by which a normal cell undergoes genetic changes that result in phenotypic alterations and the acquisition of the ability to spread and colonize distant sites in the body. Although many factors regulate malignant tumor growth and spread, interactions between a tumor and its surrounding microenvironment result in the production of important protein products that are crucial to each step of tumor progression. The matrix metalloproteinases (MMPs) are a family of degradative enzymes with clear links to malignancy. These enzymes are associated with tumor cell invasion of the basement membrane and stroma, blood vessel penetration, and metastasis. They have more recently been implicated in primary and metastatic tumor growth and angiogenesis, and they may even have a role in tumor promotion. This review outlines our current understanding of the MMP family, including the association of particular MMPs with malignant phenotypes and the role of MMPs in specific steps of the metastatic cascade. As scientific understanding of the MMPs has advanced, therapeutic strategies that capitalize on blocking the enzymes have rapidly developed. The preclinical and clinical evolution of the synthetic MMP inhibitors (MMPIs) is also examined, with the discussion encompassing important methodologic issues associated with determining clinical efficacy of MMPIs and other novel therapeutic agents.

scholarly journals The Role of Matrix Metalloproteinases in Periodontal Disease

2020 ◽  
Vol 17 (14) ◽  
pp. 4923 ◽  
Author(s):  
Vittorio Checchi ◽  
Tatjana Maravic ◽  
Pierantonio Bellini ◽  
Luigi Generali ◽  
Ugo Consolo ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Periodontal Disease ◽  
Anaerobic Bacteria ◽  
Therapeutic Strategies ◽  
Oral Diseases ◽  
Tissue Destruction ◽  
Proinflammatory Mediators ◽  
Disease Therapy ◽  
Important Pathway

This review provides a detailed description of matrix metalloproteinases (MMPs), focusing on those that are known to have critical roles in bone and periodontal disease. Periodontal disease is an inflammatory process initiated by anaerobic bacteria, which promote the host immune response in the form of a complex network of molecular pathways involving proinflammatory mediators such as cytokines, growth factors, and MMPs. MMPs are a family of 23 endopeptidases, collectively capable of degrading virtually all extracellular matrix (ECM) components. This study critically discusses the available research concerning the involvement of the MMPs in periodontal disease development and progression and presents possible therapeutic strategies. MMPs participate in morphogenesis, physiological tissue turnover, and pathological tissue destruction. Alterations in the regulation of MMP activity are implicated in the manifestation of oral diseases, and MMPs comprise the most important pathway in tissue destruction associated with periodontal disease. MMPs can be considered a risk factor for periodontal disease, and measurements of MMP levels may be useful markers for early detection of periodontitis and as a tool to assess prognostic follow-ups. Detection and inhibition of MMPs could, therefore, be useful in periodontal disease prevention or be an essential part of periodontal disease therapy, which, considering the huge incidence of the disease, may greatly improve oral health globally.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

scholarly journals An Electrostatic Net Model for the Role of Extracellular DNA in Biofilm Formation by Staphylococcus aureus

2015 ◽  
Vol 197 (24) ◽  
pp. 3779-3787 ◽  
Author(s):  
Vanina Dengler ◽  
Lucy Foulston ◽  
Alicia S. DeFrancesco ◽  
Richard Losick
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Extracellular Dna ◽  
Matrix Proteins ◽  
Exogenous Dna ◽  
Content Type ◽  
Cytoplasmic Proteins ◽  
The Matrix ◽  
Biofilm Matrix

ABSTRACTStaphylococcus aureusis an important human pathogen that can form biofilms on various surfaces. These cell communities are protected from the environment by a self-produced extracellular matrix composed of proteins, DNA, and polysaccharide. The exact compositions and roles of the different components are not fully understood. In this study, we investigated the role of extracellular DNA (eDNA) and its interaction with the recently identified cytoplasmic proteins that have a moonlighting role in the biofilm matrix. These matrix proteins associate with the cell surface upon the drop in pH that naturally occurs during biofilm formation, and we found here that this association is independent of eDNA. Conversely, the association of eDNA with the matrix was dependent on matrix proteins. Both proteinase and DNase treatments severely reduced clumping of resuspended biofilms; highlighting the importance of both proteins and eDNA in connecting cells together. By adding an excess of exogenous DNA to DNase-treated biofilm, clumping was partially restored, confirming the crucial role of eDNA in the interconnection of cells. On the basis of our results, we propose that eDNA acts as an electrostatic net, interconnecting cells surrounded by positively charged matrix proteins at a low pH.IMPORTANCEExtracellular DNA (eDNA) is an important component of the biofilm matrix of diverse bacteria, but its role in biofilm formation is not well understood. Here we report that inStaphylococcus aureus, eDNA associates with cells in a manner that depends on matrix proteins and that eDNA is required to link cells together in the biofilm. These results confirm previous studies that showed that eDNA is an important component of theS. aureusbiofilm matrix and also suggest that eDNA acts as an electrostatic net that tethers cells together via the proteinaceous layer of the biofilm matrix.

scholarly journals Role of Clathrin Light Chains in Regulating Invadopodia Formation

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 451
Author(s):  
Markus Mukenhirn ◽  
Francesco Muraca ◽  
Delia Bucher ◽  
Edgar Asberger ◽  
Elisa Cappio Barazzone ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Matrix Proteins ◽  
Light Chains ◽  
Heavy Chains ◽  
Uptake Pathway ◽  
The Matrix ◽  
Main Protein ◽  
First Time ◽  
Invadopodia Formation

One of the most fundamental processes of the cell is the uptake of molecules from the surrounding environment. Clathrin-mediated endocytosis (CME) is the best-described uptake pathway and regulates nutrient uptake, protein and lipid turnover at the plasma membrane (PM), cell signaling, cell motility and cell polarity. The main protein in CME is clathrin, which assembles as a triskelion-looking building block made of three clathrin heavy chains and three clathrin light chains. Compared to clathrin heavy chains (CHCs), the role of the two isoforms of clathrin light chains (CLCA and CLCB) is poorly understood. Here, we confirm that the simultaneous deletion of both CLCA/B causes abnormal actin structures at the ventral PM and we describe them, for the first time, as functional invadopodia rather than disorganized actin-cytoskeleton assembly sites. Their identification is based on the occurrence of common invadopodia markers as well as functional invadopodia activity characterized by an increased local proteolytic activity of the extracellular matrix proteins. We demonstrate that CLCA/B deletion impacts the intracellular trafficking and recovery of the matrix metalloproteinase 14 (MMP14) leading to its accumulation at the plasma membrane and induction of invadopodia formation. Importantly, we show that invadopodia formation can be prevented by depletion of MMP14. As such, we propose that CLCA/B regulate invadopodia formation by regulating MMP14 delivery to the plasma membrane.

scholarly journals Effects of N-Acetyl Cysteine on the Expression of Matrix Metalloproteinases 2 and 9 in the Lung Tissue of Rats Exposed to Cadmium

2020 ◽  
Keyword(s):  
Single Dose ◽  
Matrix Metalloproteinases ◽  
Lung Tissue ◽  
Continuous Exposure ◽  
Tissue Samples ◽  
Cd Toxicity ◽  
Mmp9 Expression ◽  
The Matrix ◽  
Continuous Dose

Objectives: This study aimed to investigate the effect of cadmium (Cd) on the matrix metalloproteinases (MMPs) -2 and -9 expression in the lung, and the role of N-acetylcysteine (NAC) in preserving the lung cells against Cd toxicity. Methods: The rats were randomly divided into five groups of G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd+NAC), and G5 (continuous dose of Cd+NAC). The level of Cd in the blood and lung tissue was measured by atomic absorption spectroscopy. Moreover, the expression of MMP2 and MMP9 genes was considered using RT-PCR. Results: Single and continuous exposure to Cd caused a significant increase in serum and the lung tissue of Cd in G2 (0.23±0.04 mg/L and 0.35±0.047 μg/g tissue) and G3 (0.50±0.068 mg/L and 0.81±0.063 μg/g tissue) groups, compared to other groups (P<0.001). The NAC supplementation significantly decreased Cd levels in the serum and lung tissue samples of rats exposed to single or continuous Cd (P<0.001). Furthermore, exposure to a single and continuous dose of Cd caused a significant increase in the MMP2 expression by 3.24-fold (P=0.003) and 11.9-fold (P<0.001), respectively. Additionally, single and continuous dose treatment of Cd led to a significant increase in the MMP9 expression by 3.20-fold (P=0.004) and 7.54-fold (P<0.001), respectively. The NAC treatments decreased the expression of MMP2 and MMP9 in the lung of rats exposed to single or continuous Cd. Conclusion: The Cd exposure was strongly associated with the accumulation of Cd and overexpression of MMP2 and MMP9 in the lung tissue. Moreover, the NAC can protect the lungs against Cd toxicity by decreasing Cd and down-regulating MMPs.

scholarly journals Exploring the Role of Matrix Metalloproteinases as Biomarkers in Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Silvia Terraneo ◽  
Elena Lesma ◽  
Silvia Ancona ◽  
Gianluca Imeri ◽  
Giuseppina Palumbo ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Tuberous Sclerosis ◽  
Pulmonary Disease ◽  
Tuberous Sclerosis Complex ◽  
Roc Curves ◽  
Pulmonary Involvement ◽  
Lung Cysts ◽  
Cystic Lung ◽  
The Matrix

Background: Lymphangioleiomyomatosis can develop in a sporadic form (S-LAM) or in women with tuberous sclerosis complex (TSC). The matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes potentially involved in cystic lung destruction, and in the process of migration of LAM cells. The aim of the study was to explore the role of MMP-2 and MMP-7, such as vascular endothelial growth factor (VEGF) -C and -D in women with LAM, including patients with minor pulmonary disease (i.e., &lt;10 lung cysts), and TSC with or without LAM.Methods: We evaluated 50 patients: 13 individuals affected by S-LAM, 20 with TSC-LAM, of whom six with minor pulmonary disease, and 17 with TSC without pulmonary involvement. Sixteen healthy women were used as controls.Results: MMP-2 resulted higher in LAM compared to healthy volunteers, and TSC patients (p = 0.040). MMP-7 was higher in TSC-LAM patient, with even greater values in patients with TSC-LAM minor pulmonary disease, than in S-LAM patients, and in controls (p = 0.001). VEGF-D level was lower than 800 pg/mL in all healthy controls and resulted higher in S-LAM and TSC-LAM than in TSC patients and controls (p &lt; 0.001). VEGF-C values were not statistically different in the study population (p = 0.354). The area under ROC curves (AUCs) of MMP-2, and MMP-7 for predicting LAM diagnosis were of 0.756 ± 0.079 (p = 0.004), and 0.828 ± 0.060 (p &lt; 0.001), respectively. Considering only patients with TSC, the AUCs for MMP-2, and MMP-7 in predicting LAM were 0.694 ± 0.088 (p = 0.044), and 0.713 ± 0.090 (p = 0.027), respectively.Conclusions: Our data suggest that MMP-2 and MMP-7 could be promising biomarkers for LAM diagnosis.

scholarly journals Biological Aspect of Pathophysiology for Frozen Shoulder

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Chul-Hyun Cho ◽  
Kwang-Soon Song ◽  
Beom-Soo Kim ◽  
Du Hwan Kim ◽  
Yun-Mee Lho
Keyword(s):  
Growth Factors ◽  
Matrix Metalloproteinases ◽  
Immune Cells ◽  
Frozen Shoulder ◽  
Matrix Remodeling ◽  
Biological Aspect ◽  
Novel Treatment ◽  
The Matrix ◽  
Basic Studies

It is fairly well understood that frozen shoulder involves several stages, which reflect the series of process from capsular inflammation and fibrosis to spontaneous resolution of this fibrosis. However, the underlying pathophysiologic process remains poorly determined. For this reason, management of frozen shoulder remains controversial. Determining the pathophysiological processes of frozen shoulder is a pivotal milestone in the development of novel treatment for patients with frozen shoulder. This article reviews what is known to date about the biological pathophysiology of frozen shoulder. Although articles for the pathophysiology of frozen shoulder provide inconsistent and inconclusive results, they have suggested both inflammation and fibrosis mediated by cytokines, growth factors, matrix metalloproteinases, and immune cells. Proinflammatory cytokines and growth factors released from immune cells control the action of fibroblast and matrix remodeling is regulated by the matrix metalloproteinases and their inhibitors. To improve our understanding of the disease continuum, better characterizing the biology of these processes at clearly defined stages will be needed. Further basic studies that use standardized protocols are required to more narrowly identify the role of cytokines, growth factors, matrix metalloproteinases, and immune cells. The results of these studies will provide needed clarity into the control mechanism of the pathogenesis of frozen shoulder and help identify new therapeutic targets for its treatment.

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